For these quests you must choose one faction to be loyal to. As you follow the main quest arc for a single faction, the quests for the other factions (with the exception of Independent/Yes Man quests) will fail as you gain infamy for siding against them when you progress through the quests for whichever faction you side with. The point at which you fail the other factions' quests varies depending on your actions and quests already completed. Once you side with a faction you can change to another faction's quest arc, only if you have not progressed down the preceding faction's quests to the point that you fail the other quest arcs from gaining infamy.

Completing parts of certain quests for a faction will cause you to fail other quest arcs no matter what. These are indicated in the table below. However, you can still fail quest arcs earlier than this due to infamy etc.

These quests can be completed at any time during the game and most do not contribute to the main storyline. Note that some of these quests will not be able to be completed if you have a low reputation with the associated faction.

These quests are only playable after Old World Blues is installed. The XP that is rewarded for quests is variable based upon your level when the quest is completed. The total XP split between the main storyline quests is approximately 3000 XP at levels 1-4 and 22000 XP at levels 45-50, the secondary quest XP ranges from 75 XP per quest to 550 XP per quest.